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BACKGROUND: Cornus officinalis Sieb. Et Zucc. has the efficacy of tonifying the marrow and filling up the essence, breaking up the accumulation and opening up the orifices. Our research team found that CoS extracts were protective against Aß25-35-induced memory impairment in mice. However, the pharmacodynamic components and mechanisms by which CoS improves AD have yet to be thoroughly explored and investigated. PURPOSE: This study focused on exploring the bioactive components and pharmacodynamic mechanisms of CoS aqueous extract underlying mitochondrial damage and neuroinflammation to improve Aß25-35-induced AD. METHODS: AD mouse models were generated using Aß25-35 brain injections. Different doses of CoS aqueous extract were orally administered to mice for 28 days. The cognitive function, neuronal and synaptic damage, mitochondrial damage (mitochondrial length, mitochondrial fusion fission-related protein expression), neuroglial activation, and immune inflammatory factor and ERK pathway-related protein levels of mice were assessed. The CoS aqueous extracts components were identified using UPLC-TQ/MS and screened for cellular activity. Midivi-1 (Drp1 inhibitor) or PD98059 (ERK inhibitor) was added to Aß25-35-exposed PC12 cells to assess whether CoS and its active compounds mMorB and CorE regulate mitochondrial fission through ERK/Drp1. PC12-N9 cells were cocultured to investigate whether mMorB and CorE could regulate mitochondrial division through the ERK pathway to modulate neuroinflammation. RESULTS: CoS improved exploration and memory in AD mice, reduced synaptic and mitochondrial damage in their hippocampus, and modulated disturbed mitochondrial dynamics. Moreover, CoS inhibited ERK pathway signaling and attenuated abnormal activation of glial cells and secondary immune inflammatory responses. Additionally, in vitro experiments revealed that CoS and its compounds 7ß-O-methylmorroniside (mMorB) and Cornusdiridoid E (CorE) ameliorated mitochondrial injury caused by Aß25-35 in PC12 cells through inhibition of the ERK/Drp1 pathway. Meanwhile, mMorB and CorE ameliorated cellular inflammation by inhibiting the Ras/ERK/CREB signaling pathway. CONCLUSION: CoS aqueous extract ameliorates behavioral deficits and brain damage in Aß25-35-induced AD mice by modulating the ERK pathway to attenuate mitochondrial damage and neuroinflammation, and the compounds mMorB and CorE are the therapeutically active ingredients.

Asunto(s)

Enfermedad de Alzheimer , Péptidos beta-Amiloides , Cornus , Modelos Animales de Enfermedad , Fragmentos de Péptidos , Extractos Vegetales , Animales , Péptidos beta-Amiloides/metabolismo , Ratones , Cornus/química , Enfermedad de Alzheimer/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/química , Masculino , Ratas , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Células PC12 , Hipocampo/efectos de los fármacos , Ratones Endogámicos C57BL , Sistema de Señalización de MAP Quinasas/efectos de los fármacos

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There is a lack of information on the compound profile of Cornus officinalis Sieb. et Zucc. seeds. This greatly affects their optimal utilization. In our preliminary study, we found that the extract of the seeds displayed a strong positive reaction to the FeCl3 solution, indicating the presence of polyphenols. However, to date, only nine polyphenols have been isolated. In this study, HPLC-ESI-MS/MS was employed to fully reveal the polyphenol profile of the seed extracts. A total of 90 polyphenols were identified. They were classified into nine brevifolincarboxyl tannins and their derivatives, 34 ellagitannins, 21 gallotannins, and 26 phenolic acids and their derivatives. Most of these were first identified from the seeds of C. officinalis. More importantly, five new types of tannins were reported for the first time: brevifolincarboxyl-trigalloyl-hexoside, digalloyl-dehydrohexahydroxydiphenoyl (DHHDP)-hexdside, galloyl-DHHDP-hexoside, DHHDP-hexahydroxydiphenoyl(HHDP)-galloyl-gluconic acid, and peroxide product of DHHDP-trigalloylhexoside. Moreover, the total phenolic content was as high as 79,157 ± 563 mg gallic acid equivalent per 100 g in the seeds extract. The results of this study not only enrich the structure database of tannins, but also provide invaluable aid to its further utilization in industries.

Asunto(s)

Cornus , Medicamentos Herbarios Chinos , Taninos/química , Cornus/química , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/métodos , Taninos Hidrolizables , Polifenoles , Semillas , Medicamentos Herbarios Chinos/química

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Fifteen previously undescribed minor iridoid glycosides, including four monomers and eleven dimers, were isolated from the fruits of Cornus officinalis Sieb. et Zucc. Their chemical structures were determined on the basis of spectroscopic data and chemical evidence. All of the isolated compounds were evaluated for their effects of the glucose consumption on the insulin resistant HepG2 cells, and four compounds, named cornuofficinalisides F, H, L, and O, increased the glucose consumption significantly at 10 µM, the EC50 values of them were determined to be 0.898, 1.625, 0.923, and 8.589 µM, respectively. Moreover, the four compounds could improve the ability of glucose uptake significantly in insulin resistant HepG2 cells.

Asunto(s)

Cornus , Glicósidos Iridoides/farmacología , Insulina , Glucosa

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Four novel iridoid glycosides neocornuside E-H (1-4), together with nine known ones (5-13), were isolated from fruits of Cornus officinalis. Their chemical structures were determined on the basis of spectroscopic analyses and comparing of the literature data. All of the isolated compounds were evaluated for their antidiabetic activity in insulin resistant HepG2 cells. Compounds 2, 4, 5, 8, and 12 exhibited antidiabetic activities with EC50 values of 40.12, 2.54, 70.43, 15.31, and 4.86 µM, respectively. Flow Sight cytometry analysis indicated that compounds 2, 4, 5, 8, and 12 improved the ability of 2-NBDG uptake of insulin-induced HepG2 cells.

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Cornus , Glicósidos Iridoides , Glicósidos Iridoides/farmacología , Glicósidos Iridoides/química , Hipoglucemiantes/farmacología , Cornus/química , Frutas/química , Estructura Molecular , Insulina , Glicósidos/química

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CONTEXT: Ursolic acid (UA) and acteoside (ATS) are important active components that have been used to treat Alzheimer's disease (AD) because of their neuroprotective effects, but the exact mechanism is still unclear. OBJECTIVE: Network pharmacology was used to explore the mechanism of UA + ATS in treating AD, and cell experiments were used to verify the mechanism. MATERIALS AND METHODS: UA + ATS targets and AD-related genes were retrieved from TCMSP, STITCH, SwissTargetPrediction, GeneCards, DisGeNET and GEO. Key targets were obtained by constructing protein interaction network through STRING. The neuroprotective effects of UA + ATS were verified in H2O2-treated PC12 cells. The subsequent experiments were divided into Normal, Model (H2O2 pre-treatment for 4 h), Control (H2O2+ solvent pre-treatment), UA (5 µM), ATS (40 µM), UA (5 µM) + ATS (40 µM). Then apoptosis, mitochondrial membrane potential, caspase-3 activity, ATG5, Beclin-1 protein expression and Akt, mTOR phosphorylation levels were detected. RESULTS: The key targets of UA + ATS-AD network were mainly enriched in Akt/mTOR pathway. Cell experiments showed that UA (ED50: 5 µM) + ATS (ED50: 40 µM) could protect H2O2-induced (IC50: 250 µM) nerve damage by enhancing cells viability, combating apoptosis, restoring MMP, reducing the activation of caspase-3, lessening the phosphorylation of Akt and mTOR, and increasing the expression of ATG5 and Beclin-1. CONCLUSIONS: ATS and UA regulates multiple targets, bioprocesses and signal pathways against AD pathogenesis. ATS and UA synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling.

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Fármacos Neuroprotectores , Proteínas Proto-Oncogénicas c-akt , Animales , Caspasa 3/metabolismo , Glucósidos , Peróxido de Hidrógeno/toxicidad , Farmacología en Red , Fármacos Neuroprotectores/farmacología , Ácido Oleanólico/análogos & derivados , Células PC12 , Polifenoles , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Ácido Ursólico

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Cornus officinalis, widely used in traditional Chinese medicine, exhibits pharmacological effects against erectile dysfunction and pollakisuria, which are pathological symptoms of benign prostatic hyperplasia (BPH). Although traditional usage and a study on BPH have been reported, to our knowledge, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized C. officinalis on prostatic cells. We standardized C. officinalis 30% ethanol extract (COFE) and demonstrated the therapeutic effects of COFE on human BPH epithelial cells and testosterone-induced BPH in rats. In vitro studies using BPH-1 cells demonstrated an upregulation of BPH-related and E2F Transcription Factor 1(E2F1)-dependent cell cycle markers, whereas treatment with COFE clearly inhibited the proliferation of BPH epithelial cells and reduced the overexpression of G1 and S checkpoint genes. Additionally, COFE administration alleviated the androgen-dependent prostatic enlargement in a testosterone-induced BPH animal model. COFE exerted these anti-BPH effects by the inhibition of anti-apoptotic markers, suppression of PCNA expression, and regulation of E2F1/pRB-dependent cell cycle markers in rats with BPH. These results suggest that COFE exerts anti-proliferative effect by regulating PCNA/E2F1-dependent cell cycle signaling pathway both in vivo and in vitro. These findings reveal the therapeutic potential of COFE, which could be used as a substitute for BPH treatment.

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Cornus/química , Factor de Transcripción E2F1/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Extractos Vegetales/farmacología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Próstata/metabolismo , Andrógenos/metabolismo , Animales , Biomarcadores , Ciclo Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Humanos , Masculino , Extractos Vegetales/química , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/etiología , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Ratas , Transducción de Señal/efectos de los fármacos , Testosterona/metabolismo , Testosterona/farmacología

RESUMEN

In this study, two homogeneous polysaccharides (PFC-1 and PFC-2) having anti-atherosclerotic activity were isolated from Fructus Corni. PFC-1 and PFC-2 were 1,6-α-glucans with the molecular weight of 4.4 kDa and 82.0 kDa, respectively. In the in vitro experiments, PFC-1 and PFC-2 showed significant inhibitory effects on the cholesterol accumulation in RAW264.7 macrophages induced by oxidized low-density lipoproteins (ox-LDL), and the inhibitory rate of PFC-2 was 81.62%. Apolipoprotein E-deficient (ApoE-/-) mice fed high-fat diet (HFD) were used to evaluate the anti-atherosclerotic effects of PFC-2 in vivo. The aortic root lipid area decreased by 55.01% in the PFC-2-administered group as compared to the model group. PFC-2 decreased the levels of serum low-density lipoprotein cholesterol, total cholesterol, triglycerides, and malondialdehyde, increased the superoxide dismutase activity, and reduced the contents of lipid and macrophages in the aortic sinus plaque in ApoE-/- mice fed with HFD. Furthermore, PFC-2 markedly inhibited the expression of type A1 scavenger receptor (SR-A1) and cluster of differentiation 36 (CD36) in ox-LDL-treated macrophages. Taken together, 1,6-α-glucans from Fructus Corni showed significant anti-atherogenic effect, and the mechanism is related to enhanced antioxidant activity of the ApoE-/- mice and down-regulated the expression of SR-A1 and CD36 proteins in macrophages.

Asunto(s)

Cornus/química , Glucanos/química , Glucanos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Apolipoproteínas E/genética , Aterosclerosis/tratamiento farmacológico , Biomarcadores , Supervivencia Celular/efectos de los fármacos , Colesterol/sangre , Modelos Animales de Enfermedad , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Células Espumosas/patología , Glucanos/aislamiento & purificación , Inmunohistoquímica , Lipoproteínas LDL , Espectroscopía de Resonancia Magnética , Metilación , Ratones , Ratones Noqueados , Peso Molecular , Monosacáridos/química , Extractos Vegetales/aislamiento & purificación , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Células RAW 264.7 , Análisis Espectral , Relación Estructura-Actividad

RESUMEN

BACKGROUND: Shanzhuyu (the dried mature sarcocarp of Cornus officinalis Sieb. et Zucc., DMSCO) is a Chinese herb that can be used for the treatment of Alzheimer's disease (AD), but its mechanism remains unknown. The present study aimed to investigate the active ingredients and effective mechanisms of DMSCO for the treatment of AD based on a network pharmacology approach. METHODS: The active components of DMSCO were collected from the TCMSP and ETCM databases and the target proteins of these compounds were predicted using TCMSP, SwissTargetPrediction and the STITCH database. The AD-related target proteins were identified from the OMIM, DisGeNet, GEO and GeneCards databases. The network interaction model of the compound-target-disease was established and was used to obtain the key targets of DMSCO on AD through network topology analysis. Subsequently, gene enrichment in Gene Ontology (GO) and KEGG pathways were conducted using the David 6.8 online tool. RESULTS: A total of 30 DMSCO effective compounds and 209 effective drug targets were obtained. A total of 172 AD-related genes and 37 shared targets of DMSCO and AD were identified. A total of 43 key targets for the treatment of AD were obtained from the topological analysis of the DMSCO-AD target network. These key targets were involved in a variety of biological processes, including amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress and pathways, such as the PI3K-AKT, MAPK and TNF pathways. Three key compounds, namely ursolic acid, anethole and ß-sitosterol were obtained from the analysis of the key targets. CONCLUSIONS: Ursolic acid, anethole and ß-sitosterol may be the main active components of DMSCO in the treatment of AD. DMSCO can treat AD by regulating amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress via the PI3K-AKT, MAPK and other signaling pathways.

Asunto(s)

Enfermedad de Alzheimer/tratamiento farmacológico , Cornus/química , Medicamentos Herbarios Chinos/farmacología , Derivados de Alilbenceno , Enfermedad de Alzheimer/genética , Anisoles , Humanos , Mapas de Interacción de Proteínas , Transducción de Señal , Sitoesteroles , Triterpenos , Ácido Ursólico

RESUMEN

Objective: Through network pharmacology, the network relationship between the active component of Sanqi Mixture, the target of hepatic ischemia- reperfusion injury(HIRI), and biological pathway was constructed to explore the key target and mechanism of effect of Sanqi Mixture on HIRI. Method: Through literature research at home and abroad, Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform, Pharm Mapper, Swiss Target Prediction and other servers, oral availability (OB) and drug-likeness (DL) were selected as the limited conditions to collect the relevant targets for Sanqi Mixture for intervention in HIRI. The OMIM database was used to screen and collate HIRI related genes and protein targets. Excel table was used to merge and sort the intersection between disease and targets through Cytoscape3.7.2 software plug-ins Network Analyzer, with topological parameters (degree) ≥ 5 (average degrees of freedom 4.5) for the filter to find the core targets; And the intersection targets were imported to the server STRING, and with Confidence Score of 0.85 or higher for the filter conditions to build the core protein interactions (Hub-PPI) network. The intersection target was introduced into FunRich 3.0 software for biological process and biological pathway analysis, and Cytoscape3.7.2 was used to construct the network of "traditional Chinese medicine-active ingredient-HIRI target-biological pathway". Result: Sanqi mixture could reduce the expression of Aspartate aminotransferase (AST) and glutamate transaminase (ALT) in HIRI mice (P < 0.01). After screening, 45 active components of Sanqi Mixture were obtained, corresponding to 3 273 targets, and the main compounds included ursolic acid, oleanolic acid, brucine, quercetin, ginsenoside F2, paeoniflorin, etc. Among the 196 targets obtained by HIRI, 46 targets were intersected with components, including 11-β-hydroxysteroid dehydrogenase (HSD11B1), adenosine receptor A3 (ADORA3), cyclooxygenase 2 (PTGS2), adenosine receptor A1 (ADORA1), protein kinase C-ε (PKC), etc. With the STRING server setting the qualified condition of Confidence Score ≥ 0.85, the PPI network with high Confidence was obtained and clustered into three categories through cluster processing. Five biological processes including protein metabolism, signal transduction, negative regulation of enzyme activity, inflammatory response and transmembrane receptor protein tyrosine kinase signal pathway were analyzed by FunRich software (P < 0.05). 16 biological pathways including integrin-linked kinase signal, TNF receptor signaling pathway, P38 mitogen-activated protein kinase signaling pathway, and TRAIL signaling pathway (P < 0.01). Conclusion: It is preliminarily discussed that Sanqi Mixture intervenes HIRI through the interaction of multiple components and multiple targets, as well as the regulation of multiple biological pathways and biological processes. However, the key core targets and the specific regulation mechanism still need further experimental verification.

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Objective: To clone and analyze the cDNA sequence of 3-Hydroxy-3-methylglutaryl coenzyme-a reductase (HMGR1) of Cornus officinalis. Methods: In this study, specific primers were designed at both ends of the open reading frame (ORF) based on the unigene (c100572_g1) in the transcriptome data from C. officinalis. Subsequently, the cDNA sequence of CoHMGR1 gene was amplified by RT-PCR, cloned into the pTOPO-T vector and sequenced. This gene and its encoded protein were analyzed using bioinformatics methods. Results: The results suggested that CoHMGR1 was 2 116 bp in length andthe ORF was 1 338 bp in length, which encodes 445 amino acids and is a hydrophobic protein. Multiple sequence alignment and phylogenetic analysis showed that the amino acid sequence encoded by this gene has a high similarity with that of Camptotheca acuminate, reaching 79.56%. Based on the first comparison of transcriptome sequencing from leaves and fruits of C. officinalis, the CoHMGR1 gene was successfully cloned and analyzed. Conclusion: This study laid a foundation for studying the function of CoHMGR1 protein and the molecular mechanism of terpene biosynthesis pathway of C. officinalis.

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Objective: To clone the full-length cDNA sequence of CoDXR, a key enzyme gene of Cornus officinalis, and provide a basis for further study of C. officinalis. Methods: In this study, we used the transcript sequence c147202_g1 from the transcriptome data of C. officinalis obtained in our laboratory as template, designed specific primers through Primer Premier 5.0, cloned the full-length cDNA sequence of C. officinalis DXR gene by RT-PCR technology, and the bioinformatics analysis and function prediction were carried out through the relevant bioinformatics software. Results: The results showed that the CoDXR gene was 1 505 bp in length and the ORF was 729 bp in length, encoding 242 amino acids. The results of predictive analysis of CoDXR protein by SignalP4.0Server and HMMTOP showed that the protein was a hydrophobic protein without signal peptide and transmembrane region. Phylogenetic tree analysis showed that the CoDXR protein had the highest similarity to the DXR protein sequence of Camellia sinensis. Conclusion: In this study, the key enzyme gene CoDXR was successfully cloned based on the sequencing of the C. officinalis transcriptome, and related bioinformatics analysis was carried out. The results of this study laid the foundation for further study on the function of CoDXR gene in the terpenoid synthesis pathway of C. officinalis.

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BACKGROUND: The aim of this study was to simplify and identify the contents of the herbal formula, HBX-5. This study was carried out to evaluate the therapeutic effects of HBX-6 in a mouse model of benign prostatic hyperplasia (BPH). Based on in vitro, we selected a candidate, reconstituted an experimental agent and investigated the effects on testosterone-induced BPH rats. Cell viability was determined by MTT assay in RWPE-1 and WPMY-1 cells. The expression of androgen receptor (AR) was measured in dihydrotestosterone-stimulated RWPE-1 and WPMY-1 cells. BPH was induced in mice by a subcutaneous injection of testosterone propionate for four weeks. Animals were divided into six groups: Group 1, control mice; Group 2, mice with BPH; Group 3, mice with BPH treated with finasteride; Group 4, mice with BPH treated with 200 mg/kg HBX-5; Group 5, mice with BPH treated with 100 mg/kg HBX-6; and Group 6, mice with BPH treated with 200 mg/kg HBX-6. Changes in prostate weight were measured after treatments, and the thickness of the epithelium was evaluated. The expression levels of proteins associated with prostatic cell proliferation and cell cycle-related proteins were determined. Based on previous reports and in vitro results, we selected Cornus officinalis and Psoralea corylifolia among HBX-5 components and reconstituted the experimental agent, and named it HBX-6. The result represented a new herbal formula, HBX-6 that suppressed the pathological alterations in BPH and showed a marked reduction in proliferation-related protein expression compared to mice with BPH. Our results indicate that HBX-6 has a better therapeutic effect in the BPH murine model than those of HBX-5 and finasteride, suggesting the role of HBX-6 as a new BPH remedial agent.

Asunto(s)

Cornus/química , Factor de Transcripción E2F1/antagonistas & inhibidores , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hiperplasia Prostática/metabolismo , Psoralea/química , Animales , Ciclo Celular , Línea Celular , Proliferación Celular , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/patología , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo

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Objective: Cornus officinalis is a commonly used medicinal material in our country. In the study, the CobHLH7 was cloned and analyzed, which might be closely related to the iridoid glycosides synthesis, based on the transcriptome sequencing of Cornus officinalis fruits. Methods The special primers were designed from the both sides of open reading frame of unigene c15204_g1. The total RNA was extracted and reversed transcribed into cDNA. The transcription factor CobHLH7 was cloned through RT-PCR method, and the pMD19-T cloning vector were used for sequencing. A series of bioinformatics analysis of CobHLH7 was performed by software Protparatam, ProtScale, and SOPMA etc. Results The cDNA of CobHLH7 gene was 941bp in length, encoding 266 amino acids with a molecular weight of 29 220 and isoelectric point of 6.32. The analysis of bioinformatics through SOPMA showed that the protein was a neutral unstable protein. Its advanced structure mainly was alpha helix and random coil, and the content of beta turn and extended strand were less. Multiple sequence alignments and phylogenetic trees showed that CobHLH7 protein has high homology with ILR3 of Solanum tuberosum, ILR3-like of model organism Nicotiana attenuate. Conclusion For the first time, the CobHLH7 cDNA sequence was cloned and analyzed successfully from C. officinalis, which would lay the foundation for studying its biological functions deeply.

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Objective To investigate the anti-inflammatory effect of Cornus officinalis (CO) Decotion and its refined solutions from membrane separation by using 0.05 μm inorganic ceramic membrane (CO-0.05) and 10K polysulfone hollow fiber membrane (CO-10K), and evaluate the applicability of the membrane separation technique for concentrating the anti-inflammatory compounds of C. officinalis Decotion. Methods Inflammatory model of interleukin (IL)-1β and tumor necrosis factor (TNF)-α stimulated human fibroblast-like synoviocytes (HFLS) was prepared. The CCK-8 assay and ELISA were applied to detect the effects of C. officinalis Decotion and its refined solutions on the viability of HFLS and the secretion of inflammatory cytokines, respectively. Moreover, the animal model of adjuvant arthritis (AA) was used. The SD rats were divided into six groups: control group, model (AA) group and AA groups intragastrically receiving CO (120 mg/kg), CO-0.05 (120 mg/kg), CO-10K (120 mg/kg) and TGP (0.125 mg/kg) with daily treatments for 23 days. The weight and paw swelling of rats in different groups were detected. The ELISA was used to detect secretion levels of prostaglandin E2 (PGE2), IL-1, IL-6, and TNF-α in serum. Results The production of vascular endothelial growth factor (VEGF) induced by IL-1β/TNF-α were significantly inhibited with C. officinalis Decotion and its refined solutions by membrane separation treatment (P < 0.05, 0.01, 0.001). C. officinalis Decoction and the refined solutions significantly ameliorated paw swelling and increased weight gain of AA rats (P < 0.05, 0.01, 0.001), and reduced the secretion of TNF-α, PGE2, IL-1, IL-6 in serum (P < 0.001). By comparing the inhibition efficiency of inflammatory cytokines by inorganic ceramic membrane refined solution and polysulfone hollow fiber membrane refined solution, the polysulfone hollow fiber membrane refined solution exhibited better anti-inflammatory activity. Conclusion Both of refined solutions of C. officinalis Decotion from inorganic ceramic membrane and polysulfone hollow fiber membrane separation exhibited dramatically anti-inflammtory activity. Moreover, the polysulfone hollow fiber membrane was more applicable for concentrating the anti-inflammatory compounds of C. officinalis Decotion.

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Objective To study the efficacy enhancing and toxicity reducing effects of compatibility of Aconitum carmichaeli and Cornus officinalis on chronic heart failure (CHF) rats. Methods The CHF rats was established by ip injection of adriamycin (ADM), the CHF rats were administrated tested drugs for three weeks by means of ig administration, the tested drugs included extracts of A. carmichaeli, C. officinalis, and Compound. The serum brain natriuretic peptide (BNP) level, activity of Ca2+-ATP and Na+, K+-ATP enzymes in cardiac myocytes, and cardiac histopathology were measured. Results After three weeks of modeling, the CHF rats showed signs of ascites, loss of weight, loose stool, hogback, etc. The left ventricular ejection fraction (EF) and fraction shortening (FS) decreased significantly, and the level of BNP in serum was significantly improved; Pathological changes of ventricular tissue included rupture of myocardial fibers, degeneration and necrosis of cardiomyocytes, etc. After three weeks of gavage compatibility of A. carmichaeli and C. officinalis, the general state and cardiac histopathology of the animal was obviously improved, the level of BNP in serum was reduced significantly, the activity of Na+, K+-ATP enzymes was increased significantly. No notable improvement in the above indexes was obtained after administration of A. carmichaeli and C. officinalis alone. Conclusion The compatibility of A. carmichaeli and C. officinalis can increase the activity of Na+, K+-ATP enzyme in cardiac myocytes, and improve the energy metabolism and activity of cardiac myocytes in chronic heart failure. The compatibility of A. carmichaeli and C. officinalis play the key role of enhancing efficacy and reducing toxicity.

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Cornus officinalis Sieb. et Zucc. is part of the genus Cornus of the family Cornaceae. Ripening and dry fruits (Corni Fructus) are recognized as an essential herb medicine in the traditional Chinese medicine (TCM) and have been widely used for over 2000 years. This review provides a comprehensive summary of Corni Fructus (CF), including the botany, phytochemistry, traditional use, and current pharmacological activities. According to the basic theory of TCM, CF usually participates in various Chinese medicinal formulae to exert the essential roles in replenishing liver and kidney, arresting seminal emission and sweat. Based on modern pharmacological studies, about 90 compounds have been isolated and identified from CF. In vivo and in vitro experimental studies indicate that CF exhibits extensive pharmacological activities including hypoglycemic, antioxidant, anti-inflammatory, anticancer, neuroprotective, hepatoprotective, and nephroprotective activities. However, only about 18% of chemical constituents in CF were tested. It means the potential pharmacological activities and clinical values of CF need to be further investigated.

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Objective:To investigate the effects of a herb complex extract (HCE) prepared from Cornus officinalis Sieb. Et Zucc., Eriobotrya japonica Lindley, and olive leaves on immune response of mouse spleen NK cells in vitro and in vivo analysis.Methods:The activity of natural killer (NK) cells was measured in splenocytes and YAC-1 cells. Mice were immunosuppressed using cyclophosphamide (5 mg/kg body weight). Three different doses of HCE (200, 400, and 800 mg/kg body weight) and red ginseng extract (800 mg/kg body weight) which was used as standard immunomodulatory herb were administered orally for 4 weeks. The body weight, dietary, water intake, organs (liver, thymus, and spleen) weight, completed blood count, and cytokines (tumor necrosis factor alpha, interferon gamma, and interleukin-2) production was measured.Results:At the maximum concentration of HCE, the activity of NK cells was increased by 48.5%. HCE increased liver, spleen, and thymus weights without altering numbers of white blood cells, lymphocytes, and neutrophils in a cyclophosphamide-induced immunosuppression rat model. However, HCE recovered the inhibited cytokine expression; HCE (800 mg/kg) increased cytokines levels. The results indicate the immune enhancement potential of this HCE.Conclusion:The HCE enhances immunity by increasing NK cell activity, regulating cytokine levels, and maintaining spleen weight. Therefore, it may be used as a potential immunity enhancer.

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Objective: To investigate the effects of a herb complex extract (HCE) prepared from Cornus officinalis Sieb. Et Zucc., Eriobotrya japonica Lindley, and olive leaves on immune response of mouse spleen NK cells in vitro and in vivo analysis. Methods: The activity of natural killer (NK) cells was measured in splenocytes and YAC-1 cells. Mice were immunosuppressed using cyclophosphamide (5 mg/kg body weight). Three different doses of HCE (200, 400, and 800 mg/kg body weight) and red ginseng extract (800 mg/kg body weight) which was used as standard immunomodulatory herb were administered orally for 4 weeks. The body weight, dietary, water intake, organs (liver, thymus, and spleen) weight, completed blood count, and cytokines (tumor necrosis factor alpha, interferon gamma, and interleukin-2) production was measured. Results: At the maximum concentration of HCE, the activity of NK cells was increased by 48.5%. HCE increased liver, spleen, and thymus weights without altering numbers of white blood cells, lymphocytes, and neutrophils in a cyclophosphamide-induced immunosuppression rat model. However, HCE recovered the inhibited cytokine expression; HCE (800 mg/kg) increased cytokines levels. The results indicate the immune enhancement potential of this HCE. Conclusion: The HCE enhances immunity by increasing NK cell activity, regulating cytokine levels, and maintaining spleen weight. Therefore, it may be used as a potential immunity enhancer.

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Objective: To establish a method of quantitative analysis of multi-components by single marker (QAMS) for medicinal materials and pieces of Cornus officinalis. This method was used in combination with electronic-eye and electronic-tongue technique, and the best steaming time of Cornus officinalis was selected. Methods: Medicinal materials and pieces of C. officinalis were used as the research objects. The contents of five components were determined by establishing the relative correction factor (RCF) of gallic acid, 5-hydroxymethyl furfural (5-HMF), morroniside, cornuside, and internal reference loganin in C. officinalis. Color and taste were measured by electronic eye and electronic tongue technique. The data were analyzed by principal component analysis (PCA), and the best steaming time was optimized by analyzing the results of three methods. Results: The five compounds were well separated. The RSD values of precision and reproducibility were all less than 2%. The stability was good in 24 h. The linear relationship among the concentration and peak areas of the five compounds was all linear (r ≥ 0.999 6). The average recoveries were between 98% and 100.1% and the RSD values were all less than 2%; The RCFs of loganin with the other four compounds were 0.560, 1.344, 1.255, and 0.972 in a linear range. In the principal component analysis (PCA), the sums of main components were 94.618% and 94.98% and the discrimination indexes (DI) were 98 and 93, which indicated that all the samples of C. officinalis could be distinguished well by the electronic-eye and the electronic-tongue. The results showed that the optimum steaming time of C. officinalis was 4 h. Conclusion: The best steaming time of C. officinalis can be optimized by the combination of QAMS with electronic-eye and electronic-tongue techniques.

RESUMEN

Aim To explore the protective effect of lo-ganin ( an active component in Cornus officinalis ) on podocyte injury induced by advanced glycation end products ( AGEs) and its possible mechanism. Meth-ods Mouse podocytes were cultured in vitro and di-vided into Normal group, model group ( AGEs group) , loganin group and aminoguanidine group ( set as posi-tive control) . After being incubated with loganin( final concentrations are 0. 1, 1, 10 μmol · L-1 ) for 1 h, podocytes were stimulated by AGEs of 100 mg · L-1 for 24 h. Then, the cell viability was measured by u-sing MTT method. Podocytes apoptosis was evaluated by Hoechst33342/PI staining and flow cytometry. Re-ceptors of advanced glycation end products ( RAGE ) ,desmin and apoptosis-related protein like Bax, Bcl-2, cleaved caspase-3 in podocytes were detected by Western blot. Results Loganin ameliorated podocyte injury induced by AGEs, down-regulated the expression of desmin and RAGE. Loganin also reduced the apoptotic rate of podocytes and decreased the ratio of Bax/ Bcl-2 and the expression of pro-apoptotic protein cleaved caspase-3 in podocytes. Conclusion Loganin could ameliorate podocyte injury, and its mechanism may be related to the decrease of the expression of RAGE and inhibition of the apoptotic pathway.